Therapeutic agents for treating pain, inflammation, and fever include analgesics, anti-inflammatories, and antipyretics. Non-steroidal anti-inflammatory drugs (NSAID's) are one type of such therapeutic agents. They include propionic acid derivatives, acetic acid derivatives, fenamic acid derivatives, biphenylcarbodylic acid derivatives, oxicams, and cyclooxygenase-2 (COX-2) selective NSAID's.
Propionic acids include for example ibuprofen, naproxen, and ketoprofen. Ibuprofen in particular is a widely used, well known NSAID possessing analgesic and antipyrretic properties. It has been commercially available as an over-the-counter drug in many forms for several years. Ibuprofen is chemically known as 2-(4-isobutylphenyl)-propionic acid.
NSAID's are typically administered on a once to four times daily basis, with the daily dose ranging from about 50 to about 2000 milligrams, preferably from about 100 to 1600 and most preferably from about 200 to about 1200 milligrams.
Acetaminophen is a well known analgesic, with a daily dose ranging from about 325 to about 4000 milligrams, preferably from about 650 to about 4000 milligrams. Acetaminophen was first used in medicine by Van Mering in 1893, but only since 1949 has it gained in popularity as an effective alternative to aspirin for analgesic uses in the over the counter market. The pharmacology of APAP is reviewed by B. Ameer et al., Ann. Int. Med. 87, 202 (1977). Considering the widespread use of APAP and the volume of its manufacture, both its manufacture and its use as an analgesic are well known to persons skilled in the art.
It is known to administer NSAID's, acetaminophen, and other drugs in multiple doses over 12 or 24 hours. For example, it is known to administer multiple doses containing equal amounts of ibuprofen over 12 to 24 hours. Sustained release dosage forms containing ibuprofen are also known.
Palmisano et al., Advances in Therapy, Vol. 5, No. 4, July/August 1988 reports on a study of ketoprofen and ibuprofen for treating primary dysmenorrhea. This reference discloses the use of multiple doses of ketoprofen (initial dose of 150 mg followed by subsequent doses of 75 mg) and ibuprofen (initial dose of 800 mg followed by subsequent doses of 400 mg).
It is useful to minimize the “drug exposure” of a patient. In other words, to administer the least total amount of drug that will provide the optimal beneficial therapeutic effect. In particular, it is useful to administer analgesics such as NSAIDs or acetaminophen in a regimin which provides maximal relief at minimal total dose per day of drug.
Applicants have now discovered that NSAID's or acetaminophen provided to a mammal, preferably a human, in a specific, two step dosing regimen provide improved therapeutic effect, especially pain relief, compared with known dosing regimens. In particular, an NSAID or acetaminophen is provided to the mammal, either in one dosage form or two dosage forms taken separately, in an initial dose followed by a second dose of about 3 to 5 hours later. No further NSAID or acetaminophen need be provided, yet surprisingly the therapeutic effect of the NSAID acetaminophen lasts at least about 6 hours after administration of the second dose.